ArticleNature biomedical engineering2022
Brain-wide Cas9-mediated cleavage of a gene causing familial Alzheimer's disease alleviates amyloid-related pathologies in mice.
Article in Nature biomedical engineering, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 67 citations in OpenAlex.
- Recent Advances in CRISPR/Cas Technologies for Biological Discovery, Therapeutics, and Diagnostics.Biomolecules · 2026Review
- Nucleases and Their Inhibitors: Exploring Biological Roles, Industrial Applications, and Challenges in Heterologous Expression.Biotechnology journal · 2026Review
- Brain-targeted delivery of siRNA via non-viral delivery systems, the therapeutic strategy for Alzheimer's disease-Unveiling challenges and prospects.International journal of pharmaceutics: X · 2026Review
- Application of extracellular vesicles in the CRISPR-based diagnosis and treatment: possibilities and challenges.Journal of biological engineering · 2026Review
- Focused ultrasound-mediated APOE4 knockdown in mouse brain.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Network pharmacology study on the mechanism of berberine in Alzheimer's disease model.NPJ science of food · 2025Article
- CRISPR-Cas9: bridging the gap between aging mechanisms and therapeutic advances in neurodegenerative disorders.Frontiers in cellular neuroscience · 2025Review
- Molecular Therapeutics in Development to Treat Alzheimer's Disease.Molecular diagnosis & therapy · 2025Review
- The promise of gene therapy in common types of dementia.BioImpacts : BI · 2025Review
- Mapping the therapeutic landscape of CRISPR-Cas9 for combating age-related diseases.Frontiers in genome editing · 2025Article
- SPLICER: a highly efficient base editing toolbox that enables in vivo therapeutic exon skipping.Nature communications · 2024Article
- TaqTth-hpRNA: a novel compact RNA-targeting tool for specific silencing of pathogenic mRNA.Genome biology · 2024Article
- Review
- Whole-brain in vivo base editing reverses behavioral changes in Mef2c-mutant mice.Nature neuroscience · 2024Article
- NeuroD1 Regulated Endothelial Gene Expression to Modulate Transduction of AAV-PHP.eB and Recovery Progress after Ischemic Stroke.Aging and disease · 2023Article
- Removal of a partial genomic duplication restores synaptic transmission and behavior in the MyosinVA mutant mouse Flailer.BMC biology · 2023Article
- Vector enabled CRISPR gene editing - A revolutionary strategy for targeting the diversity of brain pathologies.Coordination chemistry reviews · 2023Article
- The potential of gene editing for Huntington's disease.Trends in neurosciences · 2023Review
- Cas9-mediated replacement of expanded CAG repeats in a pig model of Huntington's disease.Nature biomedical engineering · 2023Article
- A year in review: brain barriers and brain fluids research in 2022.Fluids and barriers of the CNS · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pathology of familial Alzheimer's disease, which is caused by dominant mutations in the gene that encodes amyloid-beta precursor protein (APP) and in those that encode presenilin 1 and presenilin 2, is characterized by extracellular amyloid plaques and intracellular neurofibrillary tangles in multiple brain regions. Here we show that the brain-wide selective disruption of a mutated APP allele in transgenic mouse models carrying the human APP Swedish mutation alleviates amyloid-beta-associated pathologies for at least six months after a single intrahippocampal administration of an adeno-associated virus that encodes both Cas9 and a single-guide RNA that targets the mutation. We also show that the deposition of amyloid-beta, as well as microgliosis, neurite dystrophy and the impairment of cognitive performance, can all be ameliorated when the CRISPR-Cas9 construct is delivered intravenously via a modified adeno-associated virus that can cross the blood-brain barrier. Brain-wide disease-modifying genome editing could represent a viable strategy for the treatment of familial Alzheimer's disease and other monogenic diseases that affect multiple brain regions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.